S-(methylthio)-homocysteine (SMETH) was disclosed in Japanese Patent Publication Kokai No. 77-83710. dated Jul. 12, 1977 (C.A. 88:23393m). The patent publication, however, did not recognize the potential of SMETH as an effective therapeutic agent, particularly the potential of SMETH to function as a potent glutamine antagonist in cancer cells.
Natural antibiotics, such as 6-diazo-5-oxo-norleucine, azaserine and acivicin, are glutamine antagonists that are effective anti-cancer agents. However, these antibiotics suffer from the disadvantage of low biochemical specificity. Accordingly, there remains a need for an effective therapeutic agent with high biochemical specificity, which inhibits cellular proliferation, such as the abnormal cellular proliferation associated with cancer cells. In particular, a potent glutamine antagonist, which overcomes the disadvantage of low biochemical specificity of natural antibiotic glutamine antagonists, is desirable.
The present invention overcomes the deficiencies in the prior art by providing a potent glutamine antagonist, which forms through the combination of SMETH and the copper of a copper chelate, that inhibits cellular proliferation, such as the abnormal cellular proliferation associated with cancer cells, with a high degree of biochemical specificity. Also provided are compositions, methods of treatment, and pharmaceutical kits.